Real-World Management and Outcomes of Crizotinib-Treated ROS1-Rearranged NSCLC: A Retrospective Canadian Cohort

Abstract

The use, safety and effectiveness of crizotinib as part of the management of ROS1-rearranged NSCLC patients in a real-world Canadian clinical cohort was the focus of this retrospective review. Twenty-one ROS1-rearranged patients with advanced/metastatic disease receiving crizotinib between 2014–2020 were identified; crizotinib demonstrated tolerability and effectiveness in this population where outcomes were similar to those described in other crizotinib-treated real-world cohorts, but lower than those of the PROFILE 1001 clinical trial population. Systemic anti-cancer therapy prior to crizotinib initiation occurred in half of the study cohort, with platin-pemetrexed and immune checkpoint inhibitors being most common. Platin-pemetrexed showed good effectiveness in this cohort, but despite high prevalence of upregulated PD-L1 expression, immune checkpoint inhibitors showed poor effectiveness in his cohort. Among all systemic therapies received, crizotinib showed the most effective disease control, although longer intervals between diagnosis and crizotinib initiation were more common among those showing a lack of clinical response to crizotinib, and patients with brain metastases at the time of crizotinib initiation also showed increased diagnosis to crizotinib initiation intervals and decreased clinical response to crizotinib. This study reveals crizotinib has clinical benefit, but timely identification of ROS1-rearrangements and initiation targeted therapies appears important to maximize outcome in this population.

Development of crizotinib-associated renal cyst in a non-small cell lung cancer patient with ALK fusion: a case report and review of the literature

“…Crizotinib is the first generation of oral tyrosine kinase inhibitor that suppress the targets of ALK, ROS1, and c-met proto-oncogene product (c-MET, receptor of hepatic growth factor) [ 7 – 10 , 15 – 17 ]. Introduction of crizotinib for the treatment of NSCLC with positive ALK rearrangement significantly extended progress-free survival (PFS) for the patients [ 18 , 19 ].…”

“…Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer [ 3 , 4 ], and 3–5% of NSCLC has a gene rearrangement of analplastic lymphoma kinase ( ALK ) [ 5 , 6 ]. Crizotinib, an oral first generation tyrosine kinase inhibitor of ALK, c-ros oncogene 1 (ROS-1), and c-met proto-oncogene product (c-MET) [ 7 – 10 ], significantly increased therapeutic response and progress-free survival (PFS) in patients with advanced NSCLC with ALK fusion or rearrangement in comparison with standard chemotherapy as first-line treatment [ 11 , 12 ].…”